This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Immunological memory is a hallmark of the vertebrate immune system. The first antigenic exposure leads to a slow and modest immune response while repeat exposure, even many years later, leads to a rapid and exaggerated response that is 2-3 orders of magnitude greater than the primary. In the case of humoral immunity, the increased efficacy of recall responses is due to the production of amplified levels of antigen-specific antibody, as well as the accelerated kinetics of their production. Current dogma suggests that this is due to selective activation of long-lived antigen-specific memory B cells. A downside of restricting secondary responses solely to memory cells is that the repertoire of the memory B cell pool remains static while pathogens continue to evolve. Here we are working to determine whether during secondary responses na[unreadable]ve, antigen-specific B cells participate alongside memory cells. We are showing that immune complexes formed in vivo between the antigen and pre-existing antibodies from the primary response, activate these naive B cells, inducing them to respond with accelerated kinetics and increased magnitude. The continued recruitment of new B cell clones following each antigenic exposure enables the immune system to stay abreast of rapidly changing pathogens.